Candida Albicans (candida + albican)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Candida Albicans

  • fungal pathogen candida albican
  • pathogen candida albican
  • yeast candida albican

  • Terms modified by Candida Albicans

  • candida albican infection
  • candida albican strain

  • Selected Abstracts

    Inflammatory events as detected in cervical smears and squamous intraepithelial lesions

    Anne M. E. Roeters M.D.
    Abstract The Dutch cytological coding system, KOPAC, enables to code for eight inflammatory events, that is koilocytosis (related to human papillomavirus (HPV)), Trichomonas, dysbacteriosis [related to bacterial vaginosis (BV)], Candida, Gardnerella, Actinomyces, Chlamydia, and non-specific inflammation (leucocytosis). This study presents an analysis of 1,008,879 smears. Of each smear, the age of the woman and the reason for smear taking (screening or indication) was available. The cytoscores (per mille) for these codes were calculated. For the screening smears, the cytoscores were for koilocytosis (HPV) 2.6, for Trichomonas vaginalis 1.9, for dysbacteriosis 31.4, for Candida albicans 9.8, for Gardnerella vaginalis 0.7, for Actinomyces 6.9, for Chlamydia 0.8, and for non-specific inflammatory changes 66.4. For the calculation of the Odds Ratio (OR), normal smears were used as a reference. The cytoscores for Chlamydia and Gardnerella covaried with high grade SIL (HSIL), with an OR of 7 and 12, respectively. In addition, the OR for Trichomonas vaginalis, for dysbacteriosis, and for leucocytosis proved to be significantly high in the indication smears. This study provides an oversight of HSIL and the full range of cervical infections as detected by cytology, proving that this infectious byproduct of screening can be very valuable. Diagn. Cytopathol. 2010. © 2009 Wiley-Liss, Inc. [source]

    Rapid review of liquid-based smears as a quality control measure

    Sheryl Henderson M.Med.Sc.(Cytol.)
    Abstract The objective of this study was to investigate the effectiveness of a standardized method of rapid review (RR) of monolayer preparations for the identification of abnormalities, the presence of an endocervical component and infectious agents. A total of 200 ThinPrep (Cytyc, Boxborough, MA) slides representing the spectrum of abnormalities commonly encountered in cervical/vaginal cytologic specimens was retrieved from archive. The study set comprised 129 cases within normal limits (WNL); 36 low-grade epithelial abnormalities (LGEA); 28 high-grade epithelial abnormalities (HGEA), including 2 endocervical adenocarcinomas in situ (AIS) and 7 carcinomas. Eighteen false negative (FN) cases were also included for study. Originally missed on initial review, these cases were found to be abnormal on quality control review (17 LGEA; 1 AIS). Commonly encountered infectious agents were represented and included Candida albicans, Trichomonas vaginalis, herpes simplex virus, and Actinomyces. The slides were reviewed using a standardized method of RR (turret technique, for 60 sec) by three experienced screeners masked to the original reference diagnosis. Median sensitivity for LGEA was 70% (range, 67,72%); HGEA, 69% (range, 54,80%); and FN, 65% (range, 56,78%). Specificity remained high, median specificity for LGEA was 95%; HGEA, 97%; and FN, 100%. There was no significant overcalling of any diagnostic category. The chi-square test at P < 0.05 showed no significant difference between RR and full manual rescreen of the ThinPrep smears in this study. While no statistical difference was proven, the sensitivity measurements for all categories of abnormality were moderate due to the high proportion of atypical cases included into the study set. Abnormalities on the monolayer preparations frequently displayed fewer, smaller groups of disaggregated cells with rounded cytoplasmic outlines that were difficult to discern on RR. Interobserver variation was noted. Monolayers with a paucity of diagnostic cells and those displaying subtle nuclear atypia were often overlooked. Diagn. Cytopathol. 2004;31:141,146. © 2004 Wiley-Liss, Inc. [source]

    Cover Picture: Electrophoresis 16'2010

    ELECTROPHORESIS, Issue 16 2010
    Article first published online: 19 AUG 2010
    Issue no. 16 is a regular issue with an Emphasis on "Proteins and Proteomics" comprising 20 manuscripts distributed over 4 separate parts. Part I has 7 research articles on various aspects of proteins and proteomics including combinatorial peptide ligand library for accessing low abundance proteins, analysis of membrane proteins, proteomic profiling of human colon cancer cells, quantitative determinations of biomarkers in clinical diagnostics, recombinant factor VIII, analysis of E. coli soluble proteins, and a weakly basic amino-reactive fluorescent label for IEF of proteins and chip electrophoresis. Part II has 2 research articles dealing with the CE analysis of magnetic nanoparticles and a microfluidic magnetic bead impact for cell stimulation. Part III consists of 2 research articles dealing with on-line preconcentration in CE. Instrumentation, devices and various methodologies are described in 9 research articles, which make the content of Part IV. Featured articles include: Combinatorial peptide ligand library plasma treatment: Advantages for accessing low-abundance proteins ((doi: 10.1002/elps.201000188)) Precautions to improve the accuracy of quantitative determinations of biomarkers in clinical diagnostics ((doi: 10.1002/elps.201000243)) Rapid identification of Candida albicans in blood by combined capillary electrophoresis and fluorescence in situ hybridization ((doi: 10.1002/elps.201000138)) [source]

    Exploring the Phospholipid Biosynthetic Pathways of Aspergillus fumigatus by Computational Genome Analysis

    H. Do
    Abstract Aspergillus fumigatus causes a wide range of diseases that include mycotoxicosis, allergic reactions and systematic diseases (invasive aspergillosis) with high mortality rates. In recent years, considerable progress in the genome sequencing of this fungus has been made by an international consortium, which includes the Wellcome Trust Sanger Institute (UK) and the Institute for Genome Research (USA). A tenfold whole genome shotgun sequence assembly of A. fumigatus has been made publicly available. In this study, it was attempted to identify the genes related to the phospholipid biosynthesis from the A. fumigatus genome by a gene prediction program (GlimmerM) and to reconstruct the metabolic pathway for phospholipids of A. fumigatus. Fifteen genes related to phospholipid pathway were identified in the A. fumigatus genomic sequence. The open reading frames predicted by GlimmerM showed a high amino acid sequence similarity with the other fungal phospholipid biosynthetic genes and well-conserved functional domains. The obtained results also demonstrated that the reconstructed pathway of A. fumigatus in phospholipid biosynthesis was very similar to that of other fungi such as Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida albicans, and Neurospora crassa. Therefore it is postulated that the antifungal drugs targeted for the biosynthesis of phospholipids could also be effective against A. fumigatus. [source]

    Lysozyme as Pathogen-Recognition Protein in the Hemolymph of Galleria mellonella

    In Hee LEE
    ABSTRACT Recognition of invading micro-organisms into hemolymph is a pivotal event for triggering diverse immune mechanisms in insects. It has been known that this recognition was mediated by the binding of hemolymph proteins to pattern-molecules on the cell surface of microbes. Recently, I found that the lysozyme in the G. mellonella hemolymph has binding affinity to cell-walls of Gram (-), (±) bacteria and fungus (Candida albicans). After the hemolymph was incubated with heat-killed microbes and treated with acidic buffer containing high concentration of NaCl, several plasma proteins detached from microbes were detected by reverse phase HPLC and SDS-PAGE analyses. Of binding proteins, it was assumed that the major one might be a lysozyme, which was previously characterized in the G. mellonella hemolymph. Furthermore immunoblot analysis performed with antiserum to G. mellonella lysozyme revealed that it was a lysozyme. [source]

    The Drosophila PRR GNBP3 assembles effector complexes involved in antifungal defenses independently of its Toll -pathway activation function

    Alexey A. Matskevich
    Abstract The Drosophila Toll -signaling pathway controls the systemic antifungal host response. Gram-negative binding protein 3 (GNBP3), a member of the ,-glucan recognition protein family senses fungal infections and activates this pathway. A second detection system perceives the activity of proteolytic fungal virulence factors and redundantly activates Toll. GNBP3hades mutant flies succumb more rapidly to Candida albicans and to entomopathogenic fungal infections than WT flies, despite normal triggering of the Toll pathway via the virulence detection system. These observations suggest that GNBP3 triggers antifungal defenses that are not dependent on activation of the Toll pathway. Here, we show that GNBP3 agglutinates fungal cells. Furthermore, it can activate melanization in a Toll -independent manner. Melanization is likely to be an essential defense against some fungal infections given that the entomopathogenic fungus Beauveria bassiana inhibits the activity of the main melanization enzymes, the phenol oxidases. Finally, we show that GNBP3 assembles "attack complexes", which comprise phenoloxidase and the necrotic serpin. We propose that Drosophila GNBP3 targets fungi immediately at the inception of the infection by bringing effector molecules in direct contact with the invading microorganisms. [source]

    IL-23 and the Th17 pathway promote inflammation and impair antifungal immune resistance

    Teresa Zelante
    Abstract Although inflammation is an essential component of the protective response to fungi, its dysregulation may significantly worsen fungal diseases. We found here that the IL-23/IL-17 developmental pathway acted as a negative regulator of the Th1-mediated immune resistance to fungi and played an inflammatory role previously attributed to uncontrolled Th1 cell responses. Both inflammation and infection were exacerbated by a heightened Th17 response against Candida albicans and Aspergillus fumigatus, two major human fungal pathogens. IL-23 acted as a molecular connection between uncontrolled fungal growth and inflammation, being produced by dendritic cells in response to a high fungal burden and counter-regulating IL-12p70 production. Both IL-23 and IL-17 subverted the inflammatory program of neutrophils, which resulted in severe tissue inflammatory pathology associated with infection. Our data are the first demonstrating that the IL-23/IL-17 pathway promotes inflammation and susceptibility in an infectious disease model. As IL-23-driven inflammation promotes infection and impairs antifungal resistance, modulation of the inflammatory response represents a potential strategy to stimulate protective immune responses to fungi. See accompanying commentary: [source]

    Differential role of IL-18 and IL-12 in the host defense against disseminated Candida albicans infection

    Abstract IFN-, plays a crucial role in the defense against infection with Candida albicans. Since IL-18 and IL-12 are strong stimuli of IFN-, production, we investigated whether endogenous IL-18 and IL-12 are involved in the host defense during disseminated candidiasis. IL-18 knockout (IL-18-/-) mice, but not IL-12-/- mice, displayed an increased mortality due to C. albicans infection, accompanied by a decreased clearance of the yeasts from the kidneys late during the course of infection. Histopathology of the organs, combined with phagocyte recruitment experiments, showed a decreased influx of monocytes at the sites of Candida infection, mainly in the IL-18-/- mice. Whereas production of the chemokine KC was decreased in both IL-18-/- and IL-12-/- mice, MIP-2 production was deficient only in IL-18-/- animals, which may explain the differences in phagocyte recruitment. In addition, although IFN-, production capacity, as a parameter of the Th1-protective immunity, was reduced by 65 to 80% in the IL-12-/- mice, this defect was even more pronounced in the IL-18-/- mice (85 to 95% downmodulation). In conclusion, the anticandidal effects of endogenous IL-18 are mediated late during the infection by assuring a proper IFN-, response and promoting the infiltration of the site of infection by monocytes. [source]

    Isofusidienols: Novel Chromone-3-oxepines Produced by the Endophytic Fungus Chalara sp.

    Sandra Lösgen
    Abstract Four novel metabolites, named isofusidienol A, B, C, and D (1,4), were produced by cultures of Chalara sp. (strain 6661), an endophytic fungus isolated from Artemisia vulgaris. The unprecedented chromone-3-oxepine structure of the compounds was established by detailed spectroscopic analysis and in the case of isofusidienol A (1) verified by an X-ray analysis. Additionally, two xanthones, known 5 and its 8-chloro derivative 6, were isolated. Presumably, 5 is the biosynthetic precursor of the isofusidienols. The isofusidienols exhibit antifungal activity against Candida albicans and antibacterial activity against gram-positive and gram-negative bacteria. Inhibition of Bacillus subtilis could be achieved with less than 0.625 ,g of 1 on 6-mm filter disks in plate diffusion assays. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]

    Palladium-Catalysed Amination of Electron-Deficient or Relatively Electron-Rich Benzo[b]thienyl Bromides , Preliminary Studies of Antimicrobial Activity and SARs

    Maria-Joăo R. P. Queiroz
    Abstract Several diarylamines in the benzo[b]thiophene series were prepared in good to high yields by palladium-catalysed amination of ethyl 3-bromobenzo[b]thiophene-2-carboxylate with anilines and 5-aminoindole in the presence of Pd(OAc)2, BINAP and Cs2CO3 in toluene. The presence of the ester group at the 2-position of the benzo[b]thiophene moiety increases the yields and lowers the heating times relative to the reactions performed with 3-bromobenzo[b]thiophene. When aminopyridines were used instead of anilines, the ligand and the solvent need to be changed to XANTHPHOS and dioxane in the amination reaction. With 2-aminopyridine a one-pot C,N coupling and intramolecular cyclization involving the nitrogen atom of the pyridine ring occurred, with loss of ethanol, giving an interesting fluorescent tetracyclic heteroaromatic compound. The antimicrobial activity, the minimal inhibitory concentrations (MICs) and the structure-activity relationships (SARs) were evaluated. A selectivity with low MICs was observed against Bacillus Cereus, and good results were also obtained against Candida albicans. The acids obtained by hydrolysis of the ester group, as non-proteinogenic ,,,-unsaturated ,-amino acids, can be incorporated into peptide chains to induce conformational constraints. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source]

    Internalization of tenecin 3 by a fungal cellular process is essential for its fungicidal effect on Candida albicans

    FEBS JOURNAL, Issue 16 2001
    Dae-Hee Kim
    Tenecin 3 is a glycine-rich, antifungal protein of 78 residues isolated from the insect Tenebrio molitor larva. As an initial step towards understanding the antifungal mechanism of tenecin 3, we examined how this protein interacts with the pathogenic fungus Candida albicans to exert its antifungal action. Tenecin 3 did not induce the release of a fluorescent dye trapped in the artificial membrane vesicles and it did not perturb the membrane potential of C. albicans by the initial interaction. Fluorescence confocal microscopy and flow cytometric analysis revealed that tenecin 3 is rapidly internalized into the cytoplasmic space in energy-dependent and temperature-dependent manners. This internalization is also dependent on the ionic environment and cellular metabolic states. These results suggest that the internalization of tenecin 3 into the cytoplasm of C. albicans is mediated by a fungal cellular process. The internalized tenecin 3 is dispersed in the cytoplasm, and the loss of cell viability occurs after this internalization. [source]

    Identification and characterization of the genes for N -acetylglucosamine kinase and N -acetylglucosamine-phosphate deacetylase in the pathogenic fungus Candida albicans

    FEBS JOURNAL, Issue 8 2001
    Toshiko Yamada-Okabe
    Like bacteria and many fungi, the pathogenic fungus Candida albicans can utilize GlcNAc as a carbon source for growth. A cluster of six genes was identified in the C. albicans genome. One of the genes in the cluster was CaNAG1, which is responsible for GlcN6P deaminase and is therefore essential for GlcNAc-dependent growth. The other five genes were designated CaNAG2, CaNAG3, CaNAG4, CaNAG5 and CaNAG6. The mRNA levels of CaNAG1, CaNAG2 and CaNAG5 were significantly induced by GlcNAc, whereas those of CaNAG3, CaNAG4 and CaNAG6 were not. Neither CaNAG2 nor CaNAG5 was essential for growth, but disruption of CaNAG2 or CaNAG5 greatly retarded the growth of cells using GlcNAc as the sole carbon source. Although no homolog of CaNAG2 or CaNAG5 was found in the Saccharomyces cerevisiae genome, CaNag2p displayed sequence similarities to Escherichia coli nagA, and CaNag5p is homologous to a wide variety of hexose kinases. When expressed as a fusion protein with glutathione S -transferase (GST), CaNag5p produced GlcNAc-P from GlcNAc in the presence of ATP, whereas GST alone did not. Furthermore, the recombinant GST,CaNag2p fusion protein converted GlcNAcP, which was produced by CaNag5p, into GlcNP. These results clearly demonstrate that CaNAG2 and CaNAG5 encode GlcNAcP deacetylase and GlcNAc kinase, respectively. CaNag5p recognized glucose and mannose as substrates, whereas the recently identified human GlcNAc kinase was specific to GlcNAc. Deletion of CaNAG2 or CaNAG5 markedly, and that of CaNAG1 moderately, attenuated the virulence of C. albicans in a mouse systemic infection model. Thus, it appears that GlcNAc metabolism of C. albicans is closely associated with its virulence. [source]

    Increased tumour necrosis factor-, production, higher mannose receptor activity and ability to kill Candida by concanavalin-A-activated macrophages

    Thais Herrero Geraldino
    Abstract In a previous study, our group verified that mice pretreated with concanavalin-A (Con-A) produced more tumour necrosis factor (TNF)-, and presented greater Candida clearance from the peritoneal cavity, liver and spleen, which yielded a higher survival rate than control animals. In this work, the hypothesis that macrophages were of crucial importance in overcoming the infection was tested. Thus, peritoneal macrophages from mice pretreated for 3 days with Con-A or phosphate-buffered saline (PBS) were coincubated with CR1, CR15 and 577 isolates of Candida albicans for 0.5, 1 and 2 h. The ability of Con-activated macrophages to produce TNF-,, ingest via mannose receptors and kill all the isolates was significantly greater compared with PBS-treated macrophages, and activated macrophages exhibited a lower incidence of apoptosis, verified by binding to annexin V-fluorescein isothiocyanate. The transition of yeast cells to filamentous forms during coincubation for 2 h with control macrophages was about 73,80%, whereas in the presence of Con-A-activated macrophages, it was 35,40%. Our results suggest that a greater clearance of C. albicans infection through treatment with Con-A is probably due to the activation of macrophages, which produce more TNF-,, express more mannose receptors and are better endowed to kill ingested C. albicans. [source]

    In vitro response to Candida albicans in cultures of whole human blood from young and aged donors

    Celia Murciano
    Abstract Invasive infections with opportunistic fungi, such as Candida albicans, have become an increasing problem in aged adults in recent years. This work investigates the influence of human ageing on C. albicans recognition by toll-like receptors (TLRs), essential components of the innate immune system, using a cohort of 96 young (15,42 years) and aged (>70 years) human volunteers. No significant differences between aged and young donors were observed on (1) cell surface TLR2, TLR6 and TLR4 expression on lymphocytes, monocytes and granulocytes, (2) production of cytokines [IL-8, IL-1,, IL-6, IL-10, tumour necrosis factor (TNF)-, and IL-12p70] and prostaglandin E2 (PGE2) by whole human blood in response to C. albicans and (3) fungicidal activity of whole blood. A statistically significant higher titre of natural anti- C. albicans antibodies was found in plasma of volunteers between 80 and 95 years old when compared with other age groups, probably as a consequence of the increased levels of serum Ig that has been described in elderly subjects. Therefore, the results indicate that the increased susceptibility to C. albicans infections in the elderly is not a consequence of defects in TLRs expression or signalling, nor of an impaired fungicidal activity of blood. [source]

    Effect of suramin on the human pathogen Candida albicans: implications on the fungal development and virulence

    Lys Adriana Braga-Silva
    Abstract Candida albicans is an opportunistic pathogen that is of growing medical importance because it causes superficial, mucosal and systemic infections in susceptible individuals. Here, the effect of suramin, a polysulfonated naphthylurea derivative, on C. albicans development and virulence was evaluated. Firstly, it was demonstrated that suramin (500 ,M) arrested its growth, showing a fungicidal action dependent on cell number. Suramin treatment caused profound changes in the yeast ultrastructure as shown by transmission electron microscopy. The more important changes were the enlargement of the fungi cytoplasmic vacuoles, the appearance of yeasts with an empty cytoplasm resembling ghost cells and a reduction in cell wall thickness. Suramin also blocked the transformation of yeast cells to the germ-tube and the interaction between C. albicans and epithelial cells. In order to ascertain that the action of suramin on C. albicans growth is a general feature instead of being strain-specific, the effects of suramin on 14 oral clinical strains isolated from healthy children and HIV-positive infants were analyzed. Interestingly, the strains of C. albicans isolated from HIV-positive patients were more resistant to suramin than strains isolated from healthy patients. Altogether, the results produced here show that suramin interfered with essential fungal processes, such as growth, differentiation and interaction with host cells. [source]

    CpG oligodeoxynucleotides protect mice from lethal challenge with Candida albicans via a pathway involving tumor necrosis factor-,-dependent interleukin-12 induction

    Jung-Hwa Choi
    Abstract In this study, we have attempted to determine whether the systemic administration of CpG oligodeoxynucleotide (CpG-ODN) 1826 would protect mice against systemic lethal Candida albicans infection. CpG-ODNs were found completely to protect mice from death and also reduced the growth of C. albicans in the kidneys. The administration of CpG-ODNs resulted in early interleukin (IL)-12 mRNA expression in the kidneys and an increase in serum IL-12 levels. The protective activity of CpG-ODN was abolished in IL-12-deficient (IL-12,/,) mice, thereby indicating the IL-12-dependency inherent to the effects of CpG-ODN. The protective effect of CpG-ODN was not associated with the activity of NF-,B. Interestingly, in tumor necrosis factor (TNF)-,-deficient (TNF,/,) mice CpG-ODN neither exerted protective effects nor induced IL-12 expression. These data indicate that CpG-ODN protects animals against lethal C. albicans challenge via a pathway that involves the TNF-,-dependent induction of IL-12. [source]

    Selection and identification of anaerobic lactobacilli producing inhibitory compounds against vaginal pathogens

    Jasadee Kaewsrichan
    Abstract Two strains of Lactobacillus crispatus (15L08 and 21L07) and one strain of Lactobacillus jensenii (5L08) were selected from amongst 100 isolates from the vaginas of healthy premenopausal women for properties relevant to mucosal colonization and the production of H2O2 and/or bacteriocin-like compound. All three strains self-aggregated and adhered to vaginal epithelial cells, displacing well-known vaginal pathogens, such as Gardnerella vaginalis and Candida albicans. Lactobacillus crispatus 15L08 was characterized as a potential H2O2 producer. A high level of bacteriocin-like compound was synthesized by L. jensenii 5L08, with a bactericidal mode of action for G. vaginalis, C. albicans and Escherichia coli. However, H2O2 -dependent activity alone was not sufficient to inhibit the growth of C. albicans. Simultaneous actions of H2O2 and bacteriocin-like compound produced by lactobacilli may be important for antagonizing pathogenic bacteria. These strains of lactobacilli may be excellent candidates for eventual use as probiotics to restore the normal microbial communities in the vaginal ecosystem. [source]

    Toxicity to Candida albicans mediated by human serum and peripheral blood mononuclear cells

    Joseph M. Bliss
    Abstract This study evaluates the conditions in which peripheral blood mononuclear cells mediate toxicity to Candida albicans opsonized with heat-inactivated human serum. Serum concentrations as low as 1% resulted in 50% inhibition of C. albicans metabolic activity after incubation with peripheral blood mononuclear cells at an effector to target ratio of 8. Measurable inhibition was also achieved at lower effector to target ratios and lower serum concentrations, and at least a portion of the metabolic inhibition reflected fungal cell death. Depletion of C. albicans -specific antibody decreased the toxic effect while opsonization with purified human IgG restored toxicity, and cell,cell contact between peripheral blood mononuclear cells and fungus was required. Depletion of or enrichment for monocytes from the peripheral blood mononuclear cells preparation diminished the toxic effect and the monocytic cell line, THP-1, was likewise incapable of toxicity. These studies provide evidence that antibody augments antifungal host defense and underscore the complex interrelationship between humoral and cellular immunity in these infections. [source]

    Antibody response to Candida albicans cell wall antigens

    José L López-Ribot
    Abstract The cell wall of Candida albicans is not only the structure where many essential biological functions reside but is also a significant source of candidal antigens. The major cell wall components that elicit a response from the host immune system are proteins and glycoproteins, the latter being predominantly mannoproteins. Both carbohydrate and protein moieties are able to trigger immune responses. Proteins and glycoproteins exposed at the most external layers of the wall structure are involved in several types of interactions of fungal cells with the exocellular environment. Thus, coating of fungal cells with host antibodies has the potential to profoundly influence the host,parasite interaction by affecting antibody-mediated functions such as opsonin-enhanced phagocytosis and blocking the binding activity of fungal adhesins to host ligands. In this review we examine various members of the protein and glycoprotein fraction of the C. albicans cell wall that elicit an antibody response in vivo. Some of the studies demonstrate that certain cell wall antigens and anti-cell wall antibodies may be the basis for developing specific and sensitive serologic tests for the diagnosis of candidiasis, particularly the disseminated form. In addition, recent studies have focused on the potential of antibodies against the cell wall protein determinants in protecting the host against infection. Hence, a better understanding of the humoral response triggered by the cell wall antigens of C. albicans may provide the basis for the development of (i) effective procedures for the serodiagnosis of disseminated candidiasis, and (ii) novel prophylactic (vaccination) and therapeutic strategies to control this type of infections. [source]

    Co-administration of immunomodulator tuftsin and liposomised nystatin can combat less susceptible Candida albicans infection in temporarily neutropenic mice

    Masood A Khan
    Abstract In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to know that host factors such as degree of immunological debility as well as recovery of immune functions to normality may contribute significantly to a successful elimination of the pathogens. We demonstrated previously that concomitant delivery of antimicrobial agents and immunomodulators to the pathogen harbouring-host contributes to the complete elimination of the deep-seated fungal infections (aspergillosis and candidiasis) in animals with normal immune status. Considering that neutropenic hosts are the main targets of such infections, it can be argued about the potential of the immunomodulator-based therapy in subjects with non-functional immune system. To resolve the hypothesis, we studied the role of immunomodulator tuftsin against experimental murine candidiasis in temporarily neutropenic Balb/c mice. The neutropenic mice were challenged with an isolate of Candida albicans that was showing less susceptibility to both free and liposomised-amphotericin B. The co-administration of tuftsin increased the efficiency of liposomised-polyene antibiotics (nystatin and amphotericin B) against experimental murine candidiasis in immunocompromised Balb/c mice. Pretreatment with liposomised tuftsin prior to C. albicans infection clearly enhanced protection against candidiasis, suggesting a prophylactic role of tuftsin in normal and temporarily neutropenic animals. [source]

    Correlation between virulence of Candida albicans mutants in mice and Galleria mellonella larvae

    Marc Brennan
    Abstract Candida albicans is a dimorphic human pathogen in which the yeast to hyphal switch may be an important factor in virulence in mammals. This pathogen has recently been shown to also kill insects such as the Greater Wax Moth Galleria mellonella when injected into the haemocoel of the insect larvae. We have investigated the effect of previously characterised C. albicans mutations that influence the yeast to hyphal transition on virulence in G. mellonella larvae. There is a good correlation between the virulence of these mutants in the insect host and the virulence measured through systemic infection of mice. Although the predominant cellular species detected in G. mellonella infections is the yeast form of C. albicans, mutations that influence the hyphal transition also reduce pathogenicity in the insect. The correlation with virulence measured in the mouse infection system suggests that Galleria may provide a convenient and inexpensive model for the in vivo screening of mutants of C. albicans. [source]

    Suppression of splenic macrophage Candida albicans phagocytosis following in vivo depletion of natural killer cells in immunocompetent BALB/c mice and T-cell-deficient nude mice

    I Algarra
    Abstract The resistance of mice to systemic infections caused by Candida albicans is associated with activated splenic macrophages. In addition, there is a correlation between natural killer (NK) cell activation and the resistance to systemic candidiasis. The present study was designed to clarify the role of NK cells in the control of splenic macrophage C. albicans phagocytosis by either depleting NK cells (anti-asialo GM1 treatment) or maintaining them in an activated state (tilorone treatment) in both immunocompetent BALB/c mice and T-cell-deficient nude mice. The results of the in vitro phagocytosis assays were analyzed by flow cytometry and demonstrate the pivotal role of NK cells in controlling the capacity of splenic macrophages to phagocytose C. albicans. In summary, these data provide evidence that the NK cells are the main inducers of phagocytic activity of splenic macrophages and that they mediate the protection against C. albicans systemic infection. [source]

    HIV protease inhibitors attenuate adherence of Candida albicans to epithelial cells in vitro

    Jasmin Bekti
    Abstract Oropharyngeal candidiasis is one of the first and most commonly reported opportunistic infections of untreated AIDS patients. With the introduction of the new antiviral HAART therapy, including HIV protease inhibitors, this mucocutaneous infection is nowadays only rarely observed in treated patients. It was recently shown that HIV protease inhibitors have a direct attenuating effect on Candida albicans secreted aspartic proteinases (Saps), an investigation prompted by the fact that both Sap and HIV protease belong to the superfamily of aspartic proteinases and by the observation that mucocutaneous infections sometimes resolve even in the absence of an immunological improvement of the host. As these Saps are important fungal virulence factors and play a key role in adhesion to human epithelial cells we tried to assess the effect of the HIV protease inhibitors Ritonavir, Indinavir and Saquinavir on fungal adhesion to these cells. The effect on phagocytosis by polymorphonuclear leukocytes was also assessed. Ritonavir was found to be the most potent inhibitor of fungal adhesion. A dose-dependent inhibition of adhesion to epithelial cells was found already at 0.8 ,M and was significant at 4 ,M or higher, at 500 ,M the inhibition was about 55%. Indinavir and Saquinavir inhibited significantly at 4 ,M or 20 ,M, respectively; at 500 ,M the inhibition was 30% or 50%. In contrast, no protease inhibitor was able to modulate phagocytosis of Candida by polymorphonuclear leukocytes. In conclusion, inhibition of Saps by HIV protease inhibitors may directly help to ease the resolution of mucosal candidiasis. In future, derivatives of HIV protease inhibitors, being more specific for the fungal Saps, may form an alternative in the treatment of mucosal candidiasis insensitive to currently available antimycotics. [source]

    Measurement of blood clearance time by Limulus G test of Candida -water soluble polysaccharide fraction, CAWS, in mice

    Kiyoshi Kurihara
    Abstract The Limulus G test, responsive to ,-1,3- d -glucan, is a well-established method for the detection of invasive fungal infection. We have recently found that Candida albicans released a water-soluble polysaccharide fraction (CAWS) into synthetic medium (Uchiyama et al., FEMS Immunol. Med. Microbiol. 24 (1999) 411,420). CAWS was composed of a mannoprotein-,-glucan complex and activated Limulus factor G, and thus would be similar to the Limulus active substance in patient's blood. In a preliminary investigation, we have found that CAWS is lethal when administered intravenously in a murine system. In this study, we examined the toxicity and then the fate of CAWS in mice. The lethal toxicity was strain-dependent and strain DBA/2 was the most resistant. The toxicity was, at least in part, reduced by salbutamol sulfate and prednisolone treatment in the sensitive strains. On intravenous administration, the half clearance time (t1/2) was approximately 40 min in mice (DBA/2). On intraperitoneal administration, CAWS appeared in the blood with a peak concentration at 1 h. In order to establish a treatment plan, it is important to demonstrate the onset and the termination of deep-seated mycosis. The Limulus G test is suitable for the above purpose; however, it is necessary to fully understand the fate of ,-1,3- d -glucan in patients' blood [source]

    A rapid screening test to distinguish between Candida albicans and Candida dubliniensis using NMR spectroscopy

    Uwe Himmelreich
    Abstract Nuclear magnetic resonance (NMR) spectroscopy combined with a statistical classification strategy (SCS) successfully distinguished between Candida albicans and Candida dubliniensis. 96% of the isolates from an independent test set were identified correctly. This proves that this rapid approach is a valuable method for the identification and chemotaxonomic characterisation of closely related taxa. Most discriminatory regions were correlated with metabolite profiles, indicating biochemical differences between the two species. [source]

    Bactericidal and inhibitory effects of azole antifungal compounds on Mycobacterium smegmatis

    Colin J Jackson
    Abstract Azole antifungals are central to therapy and act by inhibiting a cytochrome P450, sterol 14-demethylase and blocking normal sterol synthesis. Our recent identification of a mycobacterial sterol biosynthetic pathway led us to probe the efficacy of a range of these compounds against Mycobacterium smegmatis. Several showed equivalent or greater inhibitory effects to those against Candida albicans, and bactericidal activity was demonstrated for four compounds, clotrimazole, econazole, miconazole and tebuconazole. The major drug used clinically, fluconazole, was ineffective. The results are discussed in the light of the world-wide spread of tuberculosis, including drug-resistant forms and the requirement for new drugs. [source]

    Adaptive tolerance to oxidative stress and the induction of antioxidant enzymatic activities in Candida albicans are independent of the Hog1 and Cap1-mediated pathways

    FEMS YEAST RESEARCH, Issue 6 2010
    Pilar Gónzalez-Párraga
    Abstract In the pathogenic yeast Candida albicans, the MAP-kinase Hog1 mediates an essential protective role against oxidative stress, a feature shared with the transcription factor Cap1. We analysed the adaptive oxidative response of strains with both elements altered. Pretreatment with gentle doses of oxidants or thermal upshifts (28,37 and 37,42 °C) improved survival in the face of high concentrations of oxidants (50 mM H2O2 or 40 mM menadione), pointing to a functional cross-protective mechanism in the mutants. The oxidative challenge promoted a marked intracellular synthesis of trehalose, although hog1 (but not cap1) cells always displayed high basal trehalose levels. Hydrogen peroxide (H2O2) induced mRNA expression of the trehalose biosynthetic genes (TPS1 and TPS2) in the tested strains. Furthermore, oxidative stress also triggered a differential activation of various antioxidant activities, whose intensity was greater after HOG1 and CAP1 deletion. The pattern of activity was dependent on the oxidant dosage applied: low concentrations of H2O2 (0.5,5 mM) clearly induced catalase and glutathione reductase (GR), whereas drastic H2O2 exposure (50 mM) increased Mn-superoxide dismutase (SOD) isozyme-mediated SOD activity. These results firmly support the existence in C. albicans of both Hog1- and Cap1-independent mechanisms against oxidative stress. [source]

    Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infection

    FEMS YEAST RESEARCH, Issue 5 2010
    Brian M. Peters
    Abstract The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy on oral tissue have been lacking. To this end, in this study, an ex vivo murine model of oral infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anticandidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host oral tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide. [source]

    Multiple effects of amprenavir against Candida albicans

    FEMS YEAST RESEARCH, Issue 2 2010
    Lys A. Braga-Silva
    Abstract Secreted aspartyl peptidases (Saps) are virulence attributes produced by Candida albicans that participate in multiple aspects of the fungal biology and pathogenesis. In the present paper, we have shown that amprenavir, a peptidase inhibitor used in HIV chemotherapy, inhibited Sap2 and growth of C. albicans and also promoted ultrastructural alterations. Esterase activity, sterol content, biofilm formation and the expression of surface mannose- and sialic acid-rich glycoconjugates were also reduced by amprenavir. [source]

    Why does Candida albicans switch?

    FEMS YEAST RESEARCH, Issue 7 2009
    David R. Soll
    Abstract White,opaque switching in Candida albicans was first discovered in 1987. Fifteen years later, and three years after the discovery of the mating system, it was demonstrated that the switch from white to opaque was an essential step in the mating process. But this latter discovery did not reveal why C. albicans had this requirement, when Saccharomyces cerevisiae and other hemiascomycetes did not. The discovery that mating-competent opaque cells signaled mating-incompetent white cells, through the release of pheromones, to become adhesive and form biofilms provided a clue to this fundamental question. Opaque cells appeared to signal white cells to form biofilms that facilitated mating by protecting the fragile gradients of the pheromone that directed chemotropism, a process necessary for fusion. Here, we explore the discoveries and observations that have led to this hypothesis, and the ancillary questions that have risen that are related to the regulation of the unique pheromone response, the evolution of this response and the relationship between pheromone-enhanced white cell biofilms and ,asexual' biofilms formed by a/, cells. This discussion, therefore, focuses on a unique and complex component of the basic biology of C. albicans that relates switching, mating and pathogenesis. [source]